Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis

Title

Other Names:

NISCH syndrome; Neonatal ichthyosis-sclerosing cholangitis syndrome; ILVASC; NISCH syndrome; Neonatal ichthyosis-sclerosing cholangitis syndrome; ILVASC; Ichthyosis-sclerosing cholangitis syndrome See More

Categories:

Congenital and Genetic Diseases; Digestive Diseases; Skin Diseases

Summary Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 59303

Disease definition

Neonatal ichthyosis-sclerosing cholangitis (NISCH syndrome) is a very rare complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis.

Epidemiology

Less than ten patients (from unrelated consanguineous Moroccan families and from Sweden) have been reported so far.

Clinical description

The ichthyosis presents with diffuse white scales sparing the skin folds, and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly, and biochemical cholestasis. Overall, the clinical picture mimics biliary atresia (see this term). Portal hypertension, patent extrahepatic bile duct obstruction and splenomegaly may also be present. Histology shows extensive fibrosis and bile duct proliferation. Leukocyte vacuolization is a common finding. The hepatic disease may have variable expressivity, ranging from a progressive disease resulting in liver failure to regression of cholestasis.

Etiology

NISCH syndrome is caused by a mutation in the CLDN1 gene coding for the tight junction protein claudin-1.

Diagnostic methods

Diagnosis is based on clinical, biochemical and histological features.

Differential diagnosis

The differential diagnosis should include Dorfman-Chanarin syndrome and other syndromic forms of ichthyosis (see these terms).

Genetic counseling

NISCH syndrome shows an autosomal recessive pattern of inheritance.

Management and treatment

Treatments aim at improving symptoms and survival. Liver transplant remains the only effective treatment in case of liver failure. Ichthyosis is managed by hydration of the skin (topical application of creams and emollient oils), retinoids and sunlight exposure.

Visit the Orphanet disease page for more resources.

Last updated: 4/1/2008

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Hepatomegaly	Very frequent (present in 80%-99% of cases)
Hypotrichosis of the scalp	Very frequent (present in 80%-99% of cases)
Ichthyosis	Very frequent (present in 80%-99% of cases)
Jaundice	Very frequent (present in 80%-99% of cases)
Scarring alopecia of scalp	Very frequent (present in 80%-99% of cases)
Sparse and thin eyebrow	Very frequent (present in 80%-99% of cases)
Sparse body hair	Very frequent (present in 80%-99% of cases)
Sparse eyelashes	Very frequent (present in 80%-99% of cases)
Splenomegaly	Very frequent (present in 80%-99% of cases)
Abnormality of dental enamel	Occasional (present in 5%-29% of cases)
Acanthosis nigricans	Occasional (present in 5%-29% of cases)
Hypodontia	Occasional (present in 5%-29% of cases)
Oligodontia	Occasional (present in 5%-29% of cases)
Portal hypertension	Occasional (present in 5%-29% of cases)
Abnormality of blood and blood-forming tissues	-
Alopecia	-
Autosomal recessive inheritance	-
Cholangitis	-
Dry skin	-
Hypoplasia of dental enamel	-
Hypotrichosis	-
Orthokeratosis	-
Parakeratosis	-

Last updated: 9/1/2017

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Do you have updated information on this condition? Let us know.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Foundation for Ichthyosis and Related Skin Types (FIRST)
2616 North Broad Street
Colmar, PA 18915
Toll-free: 800-545-3286
Telephone: 215-997-9400
E-mail: info@firstskinfoundation.org
Website: http://www.firstskinfoundation.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

DermNetNZ provides information on ichthyosis in general. DermNetNZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Pediatric Dermatology Research Alliance (PeDRA) Annual Conference Friday, October 18, 2013 - Sunday, October 20, 2013
Location: Westin O’Hare Hotel , Rosemont, IL
Description: The goals of the PEDRA annual meetings are to provide an educational platform that will enhance the research skills of PeDRA investigators and establish a forum for the critical review of research proposals developed by PeDRA disease-focused groups and to create a bridge between basic scientists and clinicians to enhance opportunities for research. Each group will identify and prioritize the clinical needs and therapeutic opportunities.

Contact: Carl C. Baker(301) 435-1240

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.